Pharmokinetics Flashcards
What is pharmacokinetics ?
Is the aspect of pharmacology which describes what the body does to the drug.
What are the principles of pharmacokinetics?
Absorbed, distributed, metabolized and excreted. (ADME)
What are the common oral dosage forms available?
Solutions Suspensions Capsules Tablets Coated tablets
Capsules
hard gelatin shell consisting of a base and a tightly fitting cap. They contain diluents and fillers to ensure their stability .
Solutions
drug delivery is the fastest via solutions
Suspensions
doses can be controlled in a smaller volume and disintegration is not required for drug release.
What are tablets?
High compression of the drug
What is dissolution?
Is the rate limiting step for the drug to reach systemic circulation. Usually seen in tablets that are taken orally.
Coated tablets
Coated modification for palatability or for delay disintegration until the drug reaches the small intestines.
What is the rate of appearance of oral drugs in the systemic circulation?
Solution, suspension, capsules, tablet, coated tablets.
What are advantages of oral administration?
Cheap, no need to sterilize, compact, multiple dose bottles, automated machine produce tablets in large quantities .
Convenient, portable, no pain, easy to take
Variety, can get the oral drugs in many types, etc solution, suspension etc
Disadvantages of using oral drugs
Limited absorption of some drugs, food may affect absorption, patient compliance is necessary , drugs may be absorbed before systemic circulation, local effect
What is the first pass effect?
Drugs absorbed orally are transported to general circulation via liver.
Why must a doctor have patient compliance while giving oral drugs?
Can’t give an unconscious patient
Two drugs that must be given in higher amount than Iv so as to avoid the first pass effect
Morphine and propranolol
One disadvantage of using oral drugs is that it may have an local effect. Why
Antibiotics that are administered oral may affect the normal bacteria flora.
How are buccal and sublingual drugs administered?
Tablets are placed in the buccal pouch or under the tongue.
Why are sublingual drugs used?
For drugs that are destroyed by gastrointestinal fluids or substantial pre-synaptic degradation.
Examples of drugs that are administered this way (sublingually)
Glyceryl trinitrate (GTN) and other nitrates
Advantage of sublingual drugs
Avoid first pass effect , rapid absorption, drug stability
Disadvantages of sublingual administration
Discomfort in holding the drug under the mouths, if any swallowed the portion must be treated as an oral dose, small doses,
Rectal administration
Is given for the treatment of local conditions e.g hemorrhoids, to achieve systemic absorption , (suitable for patients who cannot take oral medication )
In what form are rectal administration of drugs given?
Form of suppository with a variety of bases ranging from cocoa butter and polyethylene derivatives., soft gelatin capsules are also used
Advantage of rectal administration ?
By pass liver, some of the veins draining the rectal lead directly to the general circulation, useful to patients who can’t take oral tablets or younger children.
Disadvantages of rectal
Erratic absorption:
Intravenous and intra- arterial administration
Used when a rapid onset of action is required
Slow administration of Iv and IA drugs
Avoids high concentration of the drug into circulation and minimizes sudden precipitation of insoluble drugs.
Constant administration
Used for acute therapy when the drug has a narrow therapeutic range and sustained blood concentration.
When is intra- arterial administration
Is considered for anti cancer drugs,
Advantages of intravenous
Rapid, total dose ( the whole dose is delivered to the blood stream), veins relatively insensitive
Intramuscular administration
Involves injection into muscle, used to administer oil based drugs, lipophillic drugs usually gain rapid access to the capillaries,
What is a must about intramuscular administration?
Drugs must have a variability of water solubility . If the drug is not water soluble precipitation may occur on injection prior absorption e.g. The drug Valium ( diazepam)
Administration of drugs to epithelial surface
Drugs are applied to the skin to treat skin disorder or to gain entry into systemic circulation. Maybe in the form of patches or cream formulations.
What is the stratum Corneum?
Is the outermost layer of the epidermis, consisting dead cells that lack nuclei and organelles.
Disadvantages of invenous
Suitable vein, may be toxic, requires trained personel and expensive
Advantage of subcanteous
Can be given by patient e.g insulin absorption slow but usually complete
Disadvantages of subcanteous
Can be painful ,irritant drugs can cause local tissue damage, maximum of 2 ml injection thus small doses limit use.
Advantages of intramuscular
Large culex than sc, can be given
Disadvantages of intramuscular
Trained personnel ISP required for injections. The site of injection will influence the absorption. Absorption is sometime erratic, especially for poorly soluble drugs. E.g. Diazepam, phenytoin
Best site for intramuscular injection
Deltoid muscle
Inhalation
Mainly resisted to drugs that act locally on lungs.
How are inhalation drugs administered ?
By pressurized aerosols or powder inhalers e.g. Salbutamol inhaler.
Does size of particles affect inhalation?
Yes, gases are efficiently absorbed but solid and liquids are excluded if larger than 20 microns and even then only 10% is absorbed.
What is drug absorption?
The passage of the drug from its site of administration into the systemic circulation .
What does drug absorption entails?
The passing of drugs through a barrier and membrane to reach the blood or site of infection.
Lipid water partition
Ability of a drug to diffuse across membranes
An increase in the polarity of the drug ……..
Decreases the lipid water partition.
The degree of drug ionization also influences their
Lipid water partition coefficient
The proportion of the total drug concentration present in either ionized or unionized state is indicated by
Drug dissociation constant ( Henderson Hasselbalch equation.
The lower the PKA of an acidic drug the ………
Stronger the acid is
The higher the PKA of a basic drug, ……..
The stronger the base
Drugs are absorbed by one or more ways
Passive diffusion Filtration Bulk flow Active transport Facilitated diffusion Ion pair transport Endocytosis
Describe active transport
It energy dependent ( adenosine triphosphate ) movement of compounds across membranes , most often against their concentration gradient.
This process is facilitated by the reversible binding of the molecule to be transferred by a membrane carrier protein.
Example of a drug that binds by active transport
5- fluorouracil
Facilitated diffusion
Similar to active transport but no energy is needed because the passage of drugs is driven by the concentration gradient.
Passive diffusion
Passage of drugs through membranes down their concentrated gradient of the unionized moiety
A drug uses passive diffusion is
CNS depressant barbitol
Describe filtration.
Dependent on both the existence of a pressure gradient as the driving force, the size of the drug compound and the size of the membrane pore or intracellular pores.
Bulk flow
Mainly by blood flow, occurs through intercellular pores and is the main passage way of drugs across most capillary endothelial cells.
Ion pair transport
Drugs which are highly ionized pair with other ions in the GIT to become neutral ions that can pass through membrane barriers.
Endocytosis
Uptake of exogenous molecules in membrane vesicles by phagocytize uptake of particles and pinocytosis uptake of particles in a fluid phase.
Absorption from the buccal cavity and sublingual.
Does not affect the first pass effect, rate of diffusion is faster due to the unionized form of drugs, it has a extensive network of blood vessels under the tongue facilitates rapid drug absorption.
Absorption from the stomach
Epithelial lining of stomach provides a good site for absorption, low ph ionizes the drug and may effect the passage of the drug across membranes.
Absorption from the small intestines
Has villi and micro villi and a complex supply of blood and lymphatic vessels into which blood is absorbed, conditions that shorten the intestinal transmit time will affect absorption e.g diarrhoea
Absorption from the large intestines
Absorbs compounds that were not sufficiently absorbed by the small intestine.
Factors that affect GIT absorption
Gastric emptying time Intestinal motility Food Formulation factors Metabolism Blood flow in the vessels associated with the intestines .
Factors affecting absorption after parental administrationintravenous administration
No significant limiting factors are seen, ensures immediate response due to direct passage of drug into blood.
Factors affecting absorption after parental administration intramuscular and subcutaneous
Dependent on the quantity and composition of the connective tissue.
Dependent on the capillary density
Dependent on the rate of vascular perfusion of the area
Volume and osmolarity of the solution injected
Factors affecting absorption through the skin
Outer barrier of the skin ( stratum Corneum) forms a barrier against the rapid absorption through the skin.
Enhanced by pores for the passage of drug molecules.
Factors affecting absorption from the lung
Facilitated by: the large surface area of the pulmonary alveolar membranes, limited thickness of the membranes, the high. Loos flow to the alveolar region.
Name other factors that affect absorption
Disease
Age
Genetics
Disease affecting absorption
Comorbidity ( either the presence of one or more disorders (or diseases) in addition to a primary disease or disorder, or the effect of such additional disorders or diseases) and the use of other medications affect drug absorption. E.g. Impair their absorption e.g antacids and tetracyclines reduces the rate of absorption e.g. Anticholinergics
Can diarrhea affect absorption of drugs from the small intestines
Yes.
Age affecting absorption of drugs
Drug absorption is complete in an older person, although it may proceed at a slightly slower rate resulting in one or both of
Lower peak concentration
An increase in the time for the onset of drug effect
Genetics and absorption of drugs
Drugs which undergo some form of metabolism before it is absorbed into systemic circulation may be affected genetic variances in cytochrome P450 isozumes.
